NM_012154.5:c.518+54C>T

Variant names:

• chr8-140562399-G-A
• rs2292773
• NM_012154.5:c.518+54C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012154.5(AGO2):​c.518+54C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 1,556,858 control chromosomes in the GnomAD database, including 118,403 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.40 (12855 hom., cov: 33)
  • Exomes 𝑓: 0.38 (105548 hom.)
• Consequence: AGO2 NM_012154.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• Publications: 4 publications found

Genes affected

AGO2 (HGNC:3263): (argonaute RISC catalytic component 2) This gene encodes a member of the Argonaute family of proteins which play a role in RNA interference. The encoded protein is highly basic, and contains a PAZ domain and a PIWI domain. It may interact with dicer1 and play a role in short-interfering-RNA-mediated gene silencing. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

AGO2 Gene-Disease associations (from GenCC):

• Lessel-Kreienkamp syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Illumina, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012154.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGO2	NM_012154.5	MANE Select	c.518+54C>T		intron	N/A	NP_036286.2
	AGO2	NM_001164623.3		c.518+54C>T		intron	N/A	NP_001158095.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGO2	ENST00000220592.10	TSL:1 MANE Select	c.518+54C>T		intron	N/A	ENSP00000220592.5
	AGO2	ENST00000519980.5	TSL:1	c.518+54C>T		intron	N/A	ENSP00000430176.1
	AGO2	ENST00000523609.5	TSL:1	n.*103+54C>T		intron	N/A	ENSP00000430164.1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 60988 AN: 151700 Hom.: 12835 Cov.: 33

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.356

GnomAD4 exome AF: 0.380 AC: 534084 AN: 1405040 Hom.: 105548 AF XY: 0.381 AC XY: 263670 AN XY: 692452

African (AFR) AF: 0.406 AC: 13084 AN: 32206

American (AMR) AF: 0.624 AC: 24946 AN: 39992

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 7647 AN: 23614

East Asian (EAS) AF: 0.675 AC: 26183 AN: 38818

South Asian (SAS) AF: 0.467 AC: 37954 AN: 81334

European-Finnish (FIN) AF: 0.374 AC: 17440 AN: 46642

Middle Eastern (MID) AF: 0.325 AC: 1286 AN: 3954

European-Non Finnish (NFE) AF: 0.355 AC: 383217 AN: 1080646

Other (OTH) AF: 0.386 AC: 22327 AN: 57834

GnomAD4 genome AF: 0.402 AC: 61056 AN: 151818 Hom.: 12855 Cov.: 33 AF XY: 0.409 AC XY: 30377 AN XY: 74220

African (AFR) AF: 0.402 AC: 16626 AN: 41404

American (AMR) AF: 0.528 AC: 8056 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1134 AN: 3470

East Asian (EAS) AF: 0.695 AC: 3562 AN: 5128

South Asian (SAS) AF: 0.472 AC: 2274 AN: 4820

European-Finnish (FIN) AF: 0.393 AC: 4138 AN: 10524

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24173 AN: 67892

Other (OTH) AF: 0.359 AC: 756 AN: 2108

Alfa AF: 0.392 Hom.: 3483

Bravo AF: 0.414

Asia WGS AF: 0.573 AC: 1987 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.69
PhyloP100		-2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2292773; hg19: chr8-141572498;